Differing risk factors, biological variability, and lack of high-quality research studies lead to the impossibility of “genuine evidence-based clinical guidelines” for neonatal hypoglycemia. However, texts to date have described a pragmatic approach that, in the absence of high-quality evidence, should be adopted. Understanding of normal physiology should also inform practice. Blood glucose levels fall in the hours after birth in all infants. For most, the normal process of neonatal metabolic adaptation initiates glucose release and production, as well as the mobilization of alternative fuels (eg, ketone bodies) from stores so that the physiologic fall in blood glucose is tolerated. However, some infants are at risk of impaired neonatal metabolic adaptation in that blood glucose levels may not rise and the protective metabolic responses do not occur. For these infants, it is important to prevent hypoglycemia, to recognize clinically significant hypoglycemia, and to manage this situation without causing unnecessary separation of mother and infant or disruption of breastfeeding. Investigations for the underlying cause of hypoglycemia should be performed if hypoglycemia is persistent, resistant, or unexpected.

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